Medical grade nanofibrillar cellulose hydrogel, a method for treating a subject in need of treatment of body with implantable material and a method for manufacturing the medical grade nanofibrillar cellulose hydrogel

Abstract

The present disclosure provides a medical grade nanofibrilar cellulose hydrogel comprising plant-based chemically and enzymatically unmodified nanofibrillar cellulose hydrogel having a concentration of the nanofibrillar cellulose in the range of 1.4-3.4% by weight, the nanofibrillar cellulose having a number-average diameter of fibrils and/or fibril bundles of 100 nm or less, and a storage modulus in the range of 1-35 Pa. The present disclosure also provides a method for treating a subject in need of treatment of body with implantable material, and a method for manufacturing medical grade nanofibrilar cellulose hydrogel.

1 . A method for treating a subject in need of treatment of body with implantable material, the method comprising
 providing a medical grade nanofibrillar cellulose hydrogel comprising plant-based chemically and enzymatically unmodified nanofibrillar cellulose hydrogel having a concentration of the nanofibrillar cellulose in the range of 1.4-3.4% by weight, the nanofibrillar cellulose having a number-average diameter of fibrils and/or fibril bundles of 100 nm or less, and a storage modulus in the range of 1-40 Pa determined by a rotational rheometer using plate geometry at a consistency of 0.5% by weight in aqueous medium at 22±1° C. and/or a storage modulus in the range of 0.7-20 Pa determined by a rotational rheometer using vane geometry at a consistency of 0.5% by weight in aqueous medium at 22±1° C., and   injecting, implanting or inserting the medical grade nanofibrillar cellulose hydrogel into the subject's body.   
     
     
         2 . The method of  claim 1 , wherein the nanofibrillar cellulose comprises chemically and enzymatically unmodified nanofibrillar birch cellulose. 
     
     
         3 . The method of  claim 1 , wherein the nanofibrillar cellulose consists of chemically and enzymatically unmodified nanofibrillar birch cellulose. 
     
     
         4 . The method of  claim 1 , wherein the nanofibrillar cellulose has a zero-shear viscosity in the range of 1500-50000 Pa·s and a yield stress in the range of 0.5-10 Pa, determined by a rotational rheometer using plate geometry at a consistency of 0.5% by weight in aqueous medium at 22±1° C. 
     
     
         5 . The method of  claim 1 , comprising no active agents, such as therapeutic agents or bioactive agents. 
     
     
         6 . The method of  claim 1 , wherein the medical grade nanofibrillar cellulose hydrogel comprises bacterial endotoxins 5.5 EU/g (ml) or less determined according to Ph.Eur. 2.6.14. 
     
     
         7 . The method of  claim 1 , wherein the treatment of the body with the implantable material is for 28 days or more. 
     
     
         8 . The method of  claim 1 , wherein the subject is a human subject. 
     
     
         9 . The method of  claim 1 , wherein the treatment of the body is medical treatment. 
     
     
         10 . The method of  claim 1 , wherein the treatment of the body is aesthetical treatment. 
     
     
         11 . The method of  claim 1 , wherein the treatment comprises injecting, implanting or inserting the medical grade nanofibrilar cellulose hydrogel as a tissue-supporting implant into a target in the subject's body. 
     
     
         12 . The method of  claim 1 , wherein the treatment comprises injecting, implanting or inserting the medical grade nanofibrillar cellulose hydrogel as a tissue-supporting filler into a target in the subject's body. 
     
     
         13 . The method of  claim 1 , wherein the treatment comprises injecting, implanting or inserting the medical grade nanofibrillar cellulose hydrogel as a dermal filler into a target in the subject's body. 
     
     
         14 . The method of  claim 1 , wherein the treatment comprises injecting, implanting or inserting the medical grade nanofibrillar cellulose hydrogel as viscoelastic supplementation into a target in the subject's body, wherein the target is a joint, which suffers from arthritis or other joint condition. 
     
     
         15 . The method of  claim 1 , wherein the treatment comprises injecting, implanting or inserting the medical grade nanofibrillar cellulose hydrogel as a barrier agent in surgery into a target in the subject's body. 
     
     
         16 . The method of  claim 1 , wherein the medical grade nanofibrillar cellulose hydrogel is obtained from a method comprising
 providing a suspension of chemically and/or enzymatically unmodified plant-based cellulose pulp,   pre-refining the cellulose pulp suspension with a refiner to obtain a pre-refined cellulose having SR value in the range of 87-95,   dispersing the pre-refined cellulose pulp to obtain a concentration of pre-refined cellulose in the range 1.6-3.6% by weight,   disintegrating the pre-refined cellulose pulp by a disintegrating device at said concentration to obtain medical grade nanofibrillar cellulose hydrogel,   recovering the medical grade nanofibrillar cellulose hydrogel from the disintegrating device without adjusting the concentration,   to obtain nanofibrillar cellulose hydrogel having a concentration of nanofibrillar cellulose in the range of 1.4-3.4% by weight.   
     
     
         17 . The method of  claim 16 , wherein the refiner is a mill with a roll with vertical cutting bars in a container, such as a PFI type of refiner mill and/or wherein the disintegrating device comprises a microfluidizer utilizing one or more interaction chambers. 
     
     
         18 . The method of  claim 16 , wherein the cellulose comprises birch cellulose. 
     
     
         19 . The method of  claim 16 , wherein the disintegrating of the pre-refined cellulose pulp by a fluidizer comprises
 providing a microfluidizer comprising a first interaction chamber and a second interaction chamber as the disintegration device,   carrying out a first disintegration run in a first interaction chamber, and   carrying out one or more subsequent disintegration runs in a second interaction chamber having a smaller channel diameter compared to the first chamber.   
     
     
         20 . The method of  claim 16 , wherein the preparation method is carried out in the absence of active agents, and the obtained and provided medical grade nanofibrillar cellulose hydrogel comprises no active agents.